This drug has become a hot topic in some CFS circles. Whenever a topic becomes hot, I try to compare it against my microbiome model. In the past, there have been a good hit rate for those that cause some improvements  — the responders appear to be those CFS patients that happen to have a specific microbiome profile.

While Suramin has been around for over a century, there have been no studies on it’s impact on the microbiome. I can find studies on aspirin but not Suramin.

What can be inferred

“DNA-dependent RNA primase is essential for de novo primer synthesis during DNA replication in all living organisms. Bacterial DnaG primase is an attractive target for inhibition because it is essential, low in copy number and structurally distinct from eukaryotic and archaeal primases. DnaG primase is sensitive to known inhibitors including suramin and doxorubicin.” [2016]

Doxorubicin Parallels

• “However, LAB and bifidobacteria, which are key players in the intestinal microbial balance of the healthy state, might be particularly inhibited by … gemcitabine or doxorubicin.” [2016]
• “Doxorubicin (DOX) is used as a chemotherapy drug with severe carditoxicity…..In serum, perturbed metabolites include elevation of leucine, β-glucose, O-acetyl-glycoprotein, creatine, lysine, glycerin, dimethylglycine, trimethylamine-N-oxide, myo-inositol, and N-acetyl-glycoprotein, together with level decreases of acetone, lipid, lactate, glutamate, phosphocholine, acetoacetate and pyruvate. For heart, DOX exposure caused decline of lipid, lactate, leucine, alanine, glutamate, choline, xanthine, glycerin, carnitine, and fumarate, together with elevation of glutamine, creatine, inosine, taurine and malate. Metabolic changes of kidney were mainly involved in the accumulation of α-glucose, lactate, phosphocholine, betaine, threonine, choline, taurine, glycine, urea, hypoxanthine, glutamate, and nicotinamide, coupled with reduction of asparagine, valine, methionine, tyrosine, lysine, alanine, leucine, ornithine, creatine, lipid, and acetate. ” [2016] In other words — it appears to be doing a major shift in many bacteria!
• It does impact a different microbiome associated condition — Autism [2017]

DnaG

• Identification of a Ligand-Binding Site on the Staphylococcus aureus DnaG Primase C-Terminal Domain[2017].
  • Implies that it would reduce S. Aureus, a good thing
• Also found with: Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus, Bacillus anthracis and Bacillus subtilis” [2017]
  • Discovery of inhibitors of Bacillus anthracis primase DnaG [2013].
• Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG [2015].
• Evaluation of DNA primase DnaG as a potential target for antibiotics [2014].

Side Note: Why Chemotheraphy may cause remission?

I have personally meet three different former-CFS patients that went into remission from chemotheraphy. While researching above, I came across this in one of the studies which could explain why.

• “All 34 species  of lactic acid bacteria (LAB), bifidobacteria and other intestinal bacteria proved to be resistant at the highest concentrations assayed [minimum inhibitory concentrations (MICs) > 128 µg/mL] to [chemotherapeutic agents] capecitabine, cyclophosphamide, docetaxel, erlotinib, gefitinib, irinotecan and paclitaxel.” [2016]

Bottom Line

Prior to trials in humans with CFS, I really believe that a detail (genus level) study on it’s impact of a mouse microbiome is needed (at least). This is cheap and fast to do and will fill a major gap in the existing literature on this drug.

I am particularly concerned because if something goes wrong… you can’t get rid of it from your body fast:

• “Suramin is approximately 99-98% protein bound in the serum and has a half-life of 41–78 days average of 50 days ; “
• “The mechanism of action for suramin is unclear”

This feels like a Russian roulette drug because there is too little known about it. Reducing the risks (and better understanding why it works for autism etc) can be done by just doing some simple animal studies that could be published in months.

Recommendation: Do not become a guinea pig on insufficiently researched drug trials.

Addendum

Several readers referred me to the TACA 2017 talk, which is available here. My notes on this talk are below.  Note: I am not opposed to it, I do not have the rose color glass of blind hope, and want to do due scientific diligence.

• Is it caused by metabolic syndrome — I agree, the cause of the syndrome according to my model is microbiome dysfunction (thus altering the metabolites produced).
• 2:35: His focus is on just ONE of the metabolites: ATP.  I do not disagree that ATP may be one of many metabolites involved.
• 5:40: A pattern appears — there is a documented pattern of microbiome shifts with Autism.  This becomes a chicken and the egg issue quickly.
  • He cites microbiome dysfunction, from the intertwining of items, he picked ATP as the fulcrum. He describes nothing to exclude microbiome as being a valid alternative fulcrum
  • “Membranes of Escherichia coli contain an adenosine 5′-triphosphate (ATP) energy-transducing system” [1975] [2003] so if E.Coli is diminished, then ATP production is reduced.
• 20:00 — did not mention until much later that those who received Suramin very often have a rash at the injection site (mentioned in reviews on Autism sites) which means that parents may have had tells.
• 23:00 — full of personal stories — very emotional, but very subjective

Bottom line: His results did not exclude microbiome hypothesis or other theories.  From his slides, he appears to indicate that the microbiome changed with those treated.   To exclude the microbiome hypothesis, he would need to show there was no change of the microbiome and there was improvement.